This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Intrathecal topotecan will have anti-tumor activity in children with neoplastic meningitis. Primary Objectives 1. To estimate the MTD of intraventricular topotecan administered daily for 5 consecutive days. 2. To describe the toxicities and define the dose-limiting toxicity of topotecan following intraventricular administration daily for 5 consecutive days. 3. To determine if the MTD of intraventricular topotecan is also a pharmacokinetic optimal dose as defined by topotecan lactone concentrations in the cerebral CSF. Secondary Objectives 1. To provide preliminary descriptions of the anti-tumor activity of intraventricular topotecan observed in the heterogeneous diseases that will be treated in this trial. 2. To investigate MMP, VEGF, and other potential biological markers in the CSF of patients with neoplastic meningitis prior to and throughout treatment with intraventricular topotecan. 3. To further describe the CSF pharmacokinetics of topotecan following CSF administration. 4. To investigate the feasibility of central review imaging following treatment and to correlate observed effects with response to intraventricular therapy. The meninges, protected by the blood-brain barrier from the cytotoxic effects of systemic anticancer chemotherapy, are an increasingly recognized site of tumor recurrence in both children and adults. Leukemias and lymphomas are the most common cancers with a predilection for leptomeningeal dissemination. However, a variety of solid tumors including breast or small cell lung cancers;primary central nervous system tumors (CNS) such as medulloblastoma and glioma;and childhood tumors such as neuroblastoma, retinoblastoma and rhabdomyosarcoma, may also disseminate to the leptomeninges. Intrathecal administration of anticancer drugs has been an effective strategy in the treatment and prevention of leptomeningeal leukemias and lymphomas. However, intrathecal chemotherapy has not had a dramatic impact on the progression free survival for patients with neoplastic meningitis from underlying solid tumors;in part due to the extremely limited number of agents available for intrathecal administration. Therefore, the development of new intrathecal agents with novel mechanisms of action is essential.